by Astara MarchBoston (UPI) Oct 20, 2006
PGC-1a, a protein that regulates energy production in cells, has now been proven to help the brain clear itself of free radicals that damage its neurons. Since free radical build-up is found in the brains of people with Alzheimer's disease, Parkinson's disease, Huntington's chorea, and ALS (Lou Gehrig's disease), finding ways to stimulate PGC-1a production may help protect people against these devastating conditions or halt them once they have begun.

Bruce Spiegelman, lead author of the study, and his colleagues at the Dana-Farber Cancer Institute first discovered PGC-1a in 1998 and described it as a master regulator of energy production in the cells' powerhouses, the mitochondria.

Subsequent research around the world revealed that the protein also played a role in muscle function, the development of diabetes, and a variety of other metabolic processes.

PGC-1a's intervention in free radical build-up seems to be linked to its effect on the mitochondria. Free radicals, or reactive oxygen species, are a normal waste product of mitochondrial energy production. When the protein increases activity in the mitochondria, it also increases the production of antioxidants, which naturally remove free radicals from the body.

"With this mechanism, the body can speed up mitochondrial formation and at the same time suppress the creation of reactive oxygen species, which are known to be terribly damaging to the cell," Spiegelman explained. "In this respect, the cell could be compared to a self-cleaning oven -- but one that becomes less efficient with age and in certain diseases."

In their current research, the investigators exposed normal mice and mice that lacked the ability to produce PGC-1a to a nerve toxin that accelerates the production of free radicals. The mice who couldn't produce PGC-1a suffered more brain damage because they couldn't clear the radicals from their system. They then caused mouse and human brain cells cultured in the laboratory to make 40 times the normal amount of PGC-1a, and exposed them to increasing amounts of paraquat or hydrogen peroxide that cause oxidative stress and cell damage.

More brain cells with high levels of PGC-1a survived the assault than normal cells that didn't have the ability to augment their defenses.

The team is now screening drugs to find compounds that could increase PGC-1a levels in brain cells and other areas of the body, since free radical damage has also been linked to heart attacks, strokes, cancer, and aging.

Mark Mehler, director of the Institute for Brain Disorders and Neural Regeneration at the Albert Einstein College of Medicine, was enthusiastic about the work.

"This is a beautifully done study and impacts two important areas: neurodegenerative diseases that have eluded our best abilities to figure them out, and the role of the brain in peripheral energy metabolism and the regulation of body weight and food intake," Mehler told United Press International. "People with neurodegenerative diseases such as Alzheimer's and Parkinson's also have significant metabolic abnormalities, but we have not had a good mechanistic understanding of why that occurred. Now we do. PGC-1a is what's called a modular protein that binds to a series of cofactors and plays many different roles. Finding a way to modulate its expression could protect against the onset of these devastating neurological diseases and also allow us to treat the metabolic derangements that accompany them."

Joe Beckman, a member of the Linus Pauling Institute and the director of the Environmental Health Science Center at Oregon State University, told UPI he was intrigued by the study as well.

"Being able to stimulate antioxidant defenses in the brain is something we really want to be able to do," Beckman said. "This study shows us a way to help the body to increase its natural antioxidants and its ability to handle stress."

The research is published in the online issue or October 20 print issue of the journal Cell.

Slower Aging On The HorizonWashington (UPI) Oct 19, 2006
New studies on the aging process may lead to preventions that could improve quality of life and reduce healthcare costs for those over 65, researchers say. In the last century the average lifespan has increased by about 30 years. Most people spend the last years of their lives in a fragile state, Anna McCormick, director of the biology of aging program at the National Institute on Aging, said at a recent conference on Capitol Hill.

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